CORE E: STRUCTURAL AND FUNCTIONAL VISUALIZATION Samantha Butler, Core Director; Peyman Golshani, Core Co-Director; Neil Harris and Susan Bookheimer; MRI sub-core directors Abstract The Structural and Functional Visualization Core provides comprehensive imaging services to the members of UCLA Intellectual & Developmental Disabilities Research Center (IDDRC), working on any aspect of the genetic and environmentally-induced developmental diseases affecting nervous system development and function. The research ongoing in the UCLA IDDRC spans basic scientists using reductionist approaches to elucidate the mechanisms specific to intellectual developmental disabilities (IDDs) to clinicians assessing therapeutic interventions for patients. To accommodate all of their imaging requirements, we provide access to three light microscopy cores, including a microscopy suite dedicated to IDDRC researchers, human and animal MRI facilities and the technical support needed to initiate and complete any imaging analysis. The Structural and Functional Visualization Core also works to develop new technologies for visualizing biological samples and in turn provide them to IDDRC researchers. In this proposal, we are focused on [1] developing smaller lighter one-photon miniaturized fluorescent microscopes for live imaging neural activity in freely moving animals and [2] refining the methods for CLARITY and iDISCO, protocols that render tissue transparent thereby permitting unparalleled visual acuity into the complex circuitry of the brain. These techniques offer the promise of a holistic approach to imaging, permitting IDDRC researchers to translate mechanism into therapy. For example, researchers investigating a specific intellectual disorder will be able perform MRI on patients to identify the affected region of the brain, implant miniaturized microscopes in rodent models to perform Ca2+ imaging in vivo to examine how the firing patterns of specific populations of neuron are mechanistically altered by the disease, while concomitantly examining putative aberrant circuit formation using light microscopy coupled with CLARITY. Finally, this core also supports the efforts of all the other cores, offering IDDRC researchers the ability to both probe molecular and cellular function at any level from the sub- cellular to living animals and determine the consequence of therapeutic interventions.